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Antiviral Research Apr 2024Enteroviruses are a significant global health concern, causing a spectrum of diseases from the common cold to more severe conditions like hand-foot-and-mouth disease,...
The combination of pleconaril, rupintrivir, and remdesivir efficiently inhibits enterovirus infections in vitro, delaying the development of drug-resistant virus variants.
Enteroviruses are a significant global health concern, causing a spectrum of diseases from the common cold to more severe conditions like hand-foot-and-mouth disease, meningitis, myocarditis, pancreatitis, and poliomyelitis. Current treatment options for these infections are limited, underscoring the urgent need for effective therapeutic strategies. To find better treatment option we analyzed toxicity and efficacy of 12 known broad-spectrum anti-enterovirals both individually and in combinations against different enteroviruses in vitro. We identified several novel, synergistic two-drug and three-drug combinations that demonstrated significant inhibition of enterovirus infections in vitro. Specifically, the triple-drug combination of pleconaril, rupintrivir, and remdesivir exhibited remarkable efficacy against echovirus (EV) 1, EV6, EV11, and coxsackievirus (CV) B5, in human lung epithelial A549 cells. This combination surpassed the effectiveness of single-agent or dual-drug treatments, as evidenced by its ability to protect A549 cells from EV1-induced cytotoxicity across seven passages. Additionally, this triple-drug cocktail showed potent antiviral activity against EV-A71 in human intestinal organoids. Thus, our findings highlight the therapeutic potential of the pleconaril-rupintrivir-remdesivir combination as a broad-spectrum treatment option against a range of enterovirus infections. The study also paves the way towards development of strategic antiviral drug combinations with virus family coverage and high-resistance barriers.
Topics: Animals; Humans; Enterovirus A, Human; Enterovirus; Enterovirus Infections; Enterovirus B, Human; Antiviral Agents; Drug Combinations; Adenosine Monophosphate; Oxadiazoles; Pyrrolidinones; Oxazoles; Valine; Isoxazoles; Phenylalanine; Alanine
PubMed: 38417531
DOI: 10.1016/j.antiviral.2024.105842 -
Medical Decision Making : An... 2023Polio antiviral drugs (PAVDs) may provide a critical tool in the eradication endgame by stopping poliovirus infections in immunodeficient individuals who may not clear...
BACKGROUND
Polio antiviral drugs (PAVDs) may provide a critical tool in the eradication endgame by stopping poliovirus infections in immunodeficient individuals who may not clear the virus without therapeutic intervention. Although prolonged/chronic poliovirus excreters are rare, they represent a source of poliovirus reintroduction into the general population. Prior studies that assumed the successful cessation of all oral poliovirus vaccine (OPV) use estimated the potential upper bound of the incremental net benefits (INBs) of resource investments in research and development of PAVDs. However, delays in polio eradication, OPV cessation, and the development of PAVDs necessitate an updated economic analysis to reevaluate the costs and benefits of further investments in PAVDs.
METHODS
Using a global integrated model of polio transmission, immunity, vaccine dynamics, risks, and economics, we explore the risks of reintroduction of polio transmission due to immunodeficiency-related vaccine-derived poliovirus (iVDPV) excreters and reevaluate the upper bound of the INBs of PAVDs.
RESULTS
Under the current conditions, for which the use of OPV will likely continue for the foreseeable future, even with successful eradication of type 1 wild poliovirus by the end of 2023 and continued use of Sabin OPV for outbreak response, we estimate an upper bound INB of 60 million US$2019. With >100 million US$2019 already invested in PAVD development and with the introduction of novel OPVs that are less likely to revert to neurovirulence, our analysis suggests the expected INBs of PAVDs would not offset their costs.
CONCLUSIONS
While PAVDs could play an important role in the polio endgame, their expected economic benefits drop with ongoing OPV use and poliovirus transmissions. However, stakeholders may pursue the development of PAVDs as a desired product regardless of their economic benefits.HighlightsWhile polio antiviral drugs could play an important role in the polio endgame, their expected economic benefits continue to drop with delays in polio eradication and the continued use of oral poliovirus vaccines.The incremental net benefits of investments in polio antiviral drug development and screening for immunodeficiency-related circulating polioviruses are small.Limited global resources are better spent on increasing global population immunity to polioviruses to stop and prevent poliovirus transmission.
Topics: Humans; Poliomyelitis; Poliovirus; Poliovirus Vaccine, Oral; Disease Outbreaks; Antiviral Agents
PubMed: 37577803
DOI: 10.1177/0272989X231191127 -
Human Vaccines & Immunotherapeutics Dec 2023The hexavalent vaccines DT3aP-HBV-IPV/Hib and DT2aP-HBV-IPV-Hib are routinely used for primary immunization of infants against diphtheria, tetanus, pertussis, hepatitis...
The hexavalent vaccines DT3aP-HBV-IPV/Hib and DT2aP-HBV-IPV-Hib are routinely used for primary immunization of infants against diphtheria, tetanus, pertussis, hepatitis B virus, poliomyelitis, and type b. A recent publication showed that after primary immunization with these vaccines, the odds ratios of adverse reactions (ARs) were significantly lower for DT3aP-HBV-IPV/Hib than for DT2aP-HBV-IPV-Hib. Our aim is to understand the impact of the various reactogenicity profiles at country level by comparing the ARs induced by one dose of DT3aP-HBV-IPV/Hib versus DT2aP-HBV-IPV-Hib in the primary infant immunization course. A mathematical projection tool was developed to simulate vaccination of infants with both vaccines in six countries: Austria, the Czech Republic, France, Jordan, Spain, and the Netherlands. Proportions of three local and five systemic ARs of interest for both vaccines were based on findings from a previous meta-analysis of ARs in infants. The absolute risk reductions calculated ranged from 3.0% (95% confidence interval [CI]: 2.8%-3.2%) for "Swelling at the injection site, any grade" to 10.0% (95% CI: 9.5%-10.5%) for "Fever, any grade." The difference in occurrence of the AR "Fever, any grade" between vaccines in 2020 ranged from over 7,000 in Austria to over 62,000 in France. Over 5 years, this would amount to a reduction of over 150,000 ARs in Austria and over 1.4 million ARs in France when using DT3aP-HBV-IPV/Hib instead of DT2aP-HBV-IPV-Hib. In conclusion, the estimated numbers of ARs following hexavalent vaccination in six countries showed that vaccination of infants with DT3aP-HBV-IPV/Hib could lead to fewer ARs than vaccination with DT2aP-HBV-IPV-Hib.
Topics: Humans; Infant; Haemophilus influenzae type b; Hepatitis B virus; Diphtheria-Tetanus-Pertussis Vaccine; Poliovirus Vaccine, Inactivated; Hepatitis B Vaccines; Haemophilus Vaccines; Vaccines, Combined; Vaccination; Fever; Immunization Schedule
PubMed: 37102330
DOI: 10.1080/21645515.2023.2202124 -
The American Journal of Tropical... Nov 2023Combining oral (OPV) and inactivated (IPV) poliovirus vaccines prevents importation of poliovirus and emergence of circulating vaccine-derived poliovirus. We measured...
Combining oral (OPV) and inactivated (IPV) poliovirus vaccines prevents importation of poliovirus and emergence of circulating vaccine-derived poliovirus. We measured the coverage with IPV and third dose of OPV (OPV-3) and identified determinants of coverage inequality in the most at-risk populations in Ethiopia. A national survey representing 10 partly overlapping underserved populations-pastoralists, conflict-affected areas, urban slums, hard-to-reach settings, developing regions, newly formed regions, internally displaced people (IDPs), refugees, and districts neighboring international and interregional boundaries-was conducted among children 12 to 35 months old (N = 3,646). Socioeconomic inequality was measured using the concentration index (CIX) and decomposed using a regression-based approach. One-third (95% CI: 31.5-34.0%) of the children received OPV-3 and IPV. The dual coverage was below 50% in developing regions (19.2%), pastoralists (22.0%), IDPs (22.3%), districts neighboring international (24.1%) and interregional (33.3%) boundaries, refugees (27.0%), conflict-affected areas (29.3%), newly formed regions (33.5%), and hard-to-reach areas (38.9%). Conversely, coverage was better in urban slums (78%). Children from poorest households, living in villages that do not have health posts, and having limited health facility access had increased odds of not receiving the vaccines. Low paternal education, dissatisfaction with vaccination service, fear of vaccine side effects, living in female-headed households, having employed and less empowered mothers were also risk factors. IPV-OPV3 coverage favored the rich (CIX = -0.161, P < 0.001), and causes of inequality were: inaccessibility of health facilities (13.3%), dissatisfaction with vaccination service (12.8%), and maternal (4.9%) and paternal (4.9%) illiteracy. Polio vaccination coverage in the most at-risk populations in Ethiopia is suboptimal, threatening the polio eradication initiative.
Topics: Child, Preschool; Humans; Infant; Ethiopia; Poliomyelitis; Poliovirus Vaccine, Inactivated; Poliovirus Vaccine, Oral; Risk Factors; Vaccination
PubMed: 37748762
DOI: 10.4269/ajtmh.23-0319 -
The Pan African Medical Journal 2023following the spread of the COVID-19 pandemic to Nigeria, the Federal Government of Nigeria restricted human and vehicular movements to curb the spread of the disease....
INTRODUCTION
following the spread of the COVID-19 pandemic to Nigeria, the Federal Government of Nigeria restricted human and vehicular movements to curb the spread of the disease. This action had a negative impact on Acute Flaccid Paralysis (AFP) surveillance, with a resultant reduction in the number of AFP cases reported. This paper describes the impact of the COVID-19 pandemic on poliovirus surveillance in Nigeria and the proactive interventions by Nigeria´s polio program to mitigate the impact of COVID-19 on polio surveillance.
METHODS
nine innovative strategies were implemented in all 774 Local Government Areas (LGA) of the 36 states and Federal Capital Territory (FCT) of the country. These strategies were developed by the national surveillance officers and operationalized by sub-national surveillance officers with different strategies starting at different epidemiological weeks from week 14 to 23, 2020. Many of the strategy innovations were technology-based and included: the use of mobile phones to send the AFP case definition and video by WhatsApp or by SMS, the use of state-specific toll-free numbers and Mobile Telephone Network (MTN) (mobile service provider) CallerfeelTM to community informants (CI) who were the main targets of the interventions to increase case detection and reporting. Others included the use of abridged e-surveillance integrated supportive supervision (ISS) checklists, virtual monthly DSNO meetings, and batched AFP stool specimen transportation network.
RESULTS
compared to the same period in 2019, the cumulative rate of AFP case detection and reporting had gradually declined from 39.1% in January to 16.7% before the commencement of the interventions in week 20, 2020. However, the detection and reporting increased by 57.% from week 20 to week 47 compared to the same period in 2019. This is because with COVID-19, hospital visitation dropped, and the sick remained in the communities, so the CI network was relied on to detect and report AFP cases. The cumulative proportion of AFP cases reported by community informants as of week 47 increased from 13% in 2018 to 21% in 2020. This indicates an increase of 38%. Thirty-five AFP cases were detected and reported using the MTN Caller Feel strategy, while 15 cases were reported through state-specific toll-free numbers.
CONCLUSION
the implementation of the innovative strategies was able to mitigate the low AFP case detection and reporting observed at the initial stage of the COVID-19 pandemic. The use of technology facilitated reaching the CI network, which was more instrumental in detecting and reporting the cases.
Topics: Humans; COVID-19; Nigeria; Pandemics; Paralysis; Poliomyelitis; Poliovirus; Population Surveillance
PubMed: 38370097
DOI: 10.11604/pamj.supp.2023.45.2.38261 -
RoFo : Fortschritte Auf Dem Gebiete Der... Dec 2023Differential diagnosis of non-compressive cervical myelopathy encompasses a broad spectrum of inflammatory, infectious, vascular, neoplastic, neurodegenerative, and...
BACKGROUND
Differential diagnosis of non-compressive cervical myelopathy encompasses a broad spectrum of inflammatory, infectious, vascular, neoplastic, neurodegenerative, and metabolic etiologies. Although the speed of symptom onset and clinical course seem to be specific for certain neurological diseases, lesion pattern on MR imaging is a key player to confirm diagnostic considerations.
METHODS
The differentiation between acute complete transverse myelitis and acute partial transverse myelitis makes it possible to distinguish between certain entities, with the latter often being the onset of multiple sclerosis. Typical medullary MRI lesion patterns include a) longitudinal extensive transverse myelitis, b) short-range ovoid and peripheral lesions, c) polio-like appearance with involvement of the anterior horns, and d) granulomatous nodular enhancement prototypes.
RESULTS AND CONCLUSION
Cerebrospinal fluid analysis, blood culture tests, and autoimmune antibody testing are crucial for the correct interpretation of imaging findings. The combination of neuroradiological features and neurological and laboratory findings including cerebrospinal fluid analysis improves diagnostic accuracy.
KEY POINTS
· The differentiation of medullary lesion patterns, i. e., longitudinal extensive transverse, short ovoid and peripheral, polio-like, and granulomatous nodular, facilitates the diagnosis of myelitis.. · Discrimination of acute complete and acute partial transverse myelitis makes it possible to categorize different entities, with the latter frequently being the overture of multiple sclerosis (MS).. · Neuromyelitis optica spectrum disorders (NMOSD) may start as short transverse myelitis and should not be mistaken for MS.. · The combination of imaging features and neurological and laboratory findings including cerebrospinal fluid analysis improves diagnostic accuracy.. · Additional brain imaging is mandatory in suspected demyelinating, systemic autoimmune, infectious, paraneoplastic, and metabolic diseases..
Topics: Animals; Humans; Myelitis, Transverse; Diagnosis, Differential; Multiple Sclerosis; Magnetic Resonance Imaging; Poliomyelitis
PubMed: 37479218
DOI: 10.1055/a-2114-1350 -
Pathogens (Basel, Switzerland) Mar 2024Inactivated poliovirus vaccine (IPV), available since 1955, became the first vaccine to be used to protect against poliomyelitis. While the immunogenicity of IPV to... (Review)
Review
Inactivated poliovirus vaccine (IPV), available since 1955, became the first vaccine to be used to protect against poliomyelitis. While the immunogenicity of IPV to prevent paralytic poliomyelitis continues to be irrefutable, its requirement for strong containment (due to large quantities of live virus used in the manufacturing process), perceived lack of ability to induce intestinal mucosal immunity, high cost and increased complexity to administer compared to oral polio vaccine (OPV), have limited its use in the global efforts to eradicate poliomyelitis. In order to harvest the full potential of IPV, a program of work has been carried out by the Global Polio Eradication Initiative (GPEI) over the past two decades that has focused on: (1) increasing the scientific knowledge base of IPV; (2) translating new insights and evidence into programmatic action; (3) expanding the IPV manufacturing infrastructure for global demand; and (4) continuing to pursue an ambitious research program to develop more immunogenic and safer-to-produce vaccines. While the knowledge base of IPV continues to expand, further research and product development are necessary to ensure that the program priorities are met (e.g., non-infectious production through virus-like particles, non-transmissible vaccine inducing humoral and intestinal mucosal immunity and new methods for house-to-house administration through micro-needle patches and jet injectors), the discussions have largely moved from whether to how to use this vaccine most effectively. In this review, we summarize recent developments on expanding the science base of IPV and provide insight into policy development and the expansion of IPV manufacturing and production, and finally we provide an update on the current priorities.
PubMed: 38535567
DOI: 10.3390/pathogens13030224 -
Pathogens (Basel, Switzerland) Apr 2024As the Global Polio Eradication Initiative (GPEI) strategizes towards the final steps of eradication, routine immunization schedules evolve, and high-quality vaccination... (Review)
Review
As the Global Polio Eradication Initiative (GPEI) strategizes towards the final steps of eradication, routine immunization schedules evolve, and high-quality vaccination campaigns and surveillance systems remain essential. New tools are consistently being developed, such as the novel oral poliovirus vaccine to combat outbreaks more sustainably, as well as non-infectiously manufactured vaccines such as virus-like particle vaccines to eliminate the risk of resurgence of polio on the eve of a polio-free world. As the GPEI inches towards eradication, re-strategizing in the face of evolving challenges and preparing for unknown risks in the post-certification era are critical.
PubMed: 38668278
DOI: 10.3390/pathogens13040323 -
Healthcare (Basel, Switzerland) Dec 2023Individuals with late effects of poliomyelitis (LEoP) cope with various physical and psychological symptoms throughout their entire life which become more severe as they...
BACKGROUND
Individuals with late effects of poliomyelitis (LEoP) cope with various physical and psychological symptoms throughout their entire life which become more severe as they are ageing.
OBJECTIVES
To perform a 10-year follow-up of the functional status and levels of psychological health of individuals with LEoP and to examine the associations of hope levels, work status, health perceptions, and life satisfaction with functional and psychological changes.
DESIGN
A within-subject 10-year follow-up study.
PARTICIPANTS
Eighty-two individuals with LEoP who participated in a previous study 10 years ago.
METHODS
Outcome measures included the functional status of individuals with LEoP assessed by the activities of daily living (ADL) questionnaire, emotional distress based on the Global Health Questionnaire (GHQ), hope based on the Hope Scale, life satisfaction as measured by the Satisfaction with Life Scale (SWLS), and subjective health perception. The McNemar test, paired -test, Spearman's correlation coefficient, and linear regression were used for statistical analysis.
RESULTS
The mean age was 66.9 ± 8.5 years with a male-female ratio of 0.52. A significant functional deterioration was noticed during the follow-up years. Yet, the functional deterioration was not associated with changes in psychological health. Psychological health was associated with elevated levels of hope and life satisfaction. Individuals with LEoP who continued to work demonstrated higher psychological health, higher levels of hope, and greater life satisfaction.
CONCLUSIONS
Individuals with LEoP demonstrated significant psychological health, manifested in their ability to block emotional distress and maintain life satisfaction despite the deterioration in their functional status. Hope and psychological health were associated with increased life satisfaction. Work appeared to be a significant source of psychological health in this population.
PubMed: 38132034
DOI: 10.3390/healthcare11243144 -
Vaccine Nov 2023Many western countries are challenged by delayed and insufficient vaccination coverage rates in children, and thus missing WHO coverage targets. This study aimed to... (Observational Study)
Observational Study
AIMS
Many western countries are challenged by delayed and insufficient vaccination coverage rates in children, and thus missing WHO coverage targets. This study aimed to estimate vaccination coverage and timeliness in Swiss children over a decade. Furthermore, we evaluated the impact of COVID-19, regional variations, and the adherence to the amended vaccination schedule in 2019.
METHODS
Retrospective observational study with Swiss health insurance claims data including birth cohorts 2012-2021 of children continuously observed until ages 13, 25, and 48 months respectively. We used population-weighted proportions and time-to-event analyses to describe coverage and timeliness of diphtheria/tetanus/pertussis/poliomyelitis/haemophilus influenzae type b (DTaP-IPV-Hib), measles/mumps/rubella (MMR), hepatitis B (HBV), pneumococcal (PCV), and meningococcal (MCV) vaccinations according to the national schedule. The potential impact of COVID-19 and vaccination schedule adherence were evaluated descriptively. Logistic regression was used to investigate regional factors potentially associated with non-vaccination.
RESULTS
120,073 children, representing between 12 and 17 % of all Swiss children born in corresponding years, were included. Coverage remained stable or improved over the years. The 2019 amendment of the national immunization schedule was associated with an increase of ~10 % points in full coverage in Swiss children for DTaP-IPV-Hib, MMR and HBV despite the concurrent COVID-19 pandemic. Nonetheless, full vaccination coverage remained below 90 % with many vaccination series being delayed or not completed. The comparison across the different vaccines revealed large differences in coverage. Moreover, we observed large regional differences in non-vaccination with children living in rural and German-speaking areas more likely to be entirely unvaccinated.
CONCLUSION
Full vaccination coverage in Swiss children is still below 90 % with many vaccinations administered delayed. Given regional differences, missed or delayed booster vaccinations, and differences in vaccine-specific acceptability, more effort may be needed to achieve national vaccination targets.
Topics: Child; Humans; Infant; Vaccination Coverage; Birth Cohort; Pandemics; Switzerland; Diphtheria-Tetanus-Pertussis Vaccine; Vaccination; Rubella Vaccine; Immunization Schedule; Haemophilus Vaccines; COVID-19
PubMed: 38593195
DOI: 10.1016/j.vaccine.2023.10.043